Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with 'pleasurable buzz' during early experimentation with smoking.
paper
Cited
Public
- Authors
- Sherva, Richard; Wilhelmsen, Kirk; Pomerleau, Cynthia S; Chasse, Scott A; Rice, John P; Snedecor, Sandy M; Bierut, Laura J; Neuman, Rosalind J; Pomerleau, Ovide F
- Year
- 2008
- Journal
- Addiction (Abingdon, England)
- PMID
- 18783506
- DOI
- 10.1111/j.1360-0443.2008.02279.x
- PMCID
- PMC2582398
AIMS: To extend the previously identified association between a single nucleotide polymorphism (SNP) in neuronal acetylcholine receptor subunit alpha-5 (CHRNA5) and nicotine dependence to current smoking and initial smoking-experience phenotypes. DESIGN, SETTING, PARTICIPANTS: Case-control association study with a community-based sample, comprising 363 Caucasians and 72 African Americans (203 cases, 232 controls). MEASUREMENTS: Cases had smoked > or = five cigarettes/day for > or = 5 years and had smoked at their current rate for the past 6 months. Controls had smoked between one and 100 cigarettes in their life-time, but never regularly. Participants also rated, retrospectively, pleasurable and displeasurable sensations experienced when they first smoked. We tested for associations between smoking phenotypes and the top 25 SNPs tested for association with nicotine dependence in a previous study. FINDINGS: A non-synonymous coding SNP in CHRNA5, rs16969968, was associated with case status [odds ratio (OR) = 1.5, P = 0.01] and, in Caucasians, with experiencing a pleasurable rush or buzz during the first cigarette (OR = 1.6, P = 0.01); these sensations were associated highly with current smoking (OR = 8.2, P = 0.0001). CONCLUSIONS: We replicated the observation that the minor allele of rs16969968 affects smoking behavior, and extended these findings to sensitivity to smoking effects upon experimentation. While the ability to test genetic associations was limited by sample size, the polymorphism in the CHRNA5 subunit was shown to be associated significantly with enhanced pleasurable responses to initial cigarettes in regular smokers in an a priori test. The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence.
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| Name | Type |
|---|---|
| addiction | phenotype |
| adolescents | cohort |
| adults | cohort |
| Affymetrix Kit Control DNA local | drug |
| African American | cohort |
| AIMs | variant |
| alcohol | phenotype |
| alcohol abuse | phenotype |
| Ambiguous ethnicity participants local | cohort |
| American adults | cohort |
| Asian | cohort |
| Berretinini et al. study local | cohort |
| Bierut et al. study local | cohort |
| bipolar disorder | phenotype |
| buzz local | phenotype |
| cases | cohort |
| Caucasian | cohort |
| Caucasians | cohort |
| Center for Epidemiological StudiesβDepression local | phenotype |
| Chinese adolescents local | cohort |
| Chrna3 | gene |
| CHRNA5 | gene |
| CHRNA5 amino acid variant local | variant |
| Chrna6 | gene |
| Chrnb2 | gene |
| Chrnb3 | gene |
| Chrnb4 | gene |
| cigarettes | phenotype |
| combined sample (Caucasians plus African Americans) local | cohort |
| Composite International Diagnostic Interview local | phenotype |
| controls | cohort |
| cough local | phenotype |
| current smoking | phenotype |
| ddH2O | drug |
| depression | phenotype |
| Difficulty inhaling local | phenotype |
| dizziness | phenotype |
| early smoking experience local | phenotype |
| Early smoking experiences local | phenotype |
| Early Smoking Experiences Questionnaire local | cohort |
| Early smoking sensitivity local | phenotype |
| early subjective experiences local | phenotype |
| FagerstrΓΆm Test for Nicotine Dependence | phenotype |
| genetic variants | cohort |
| Global displeasurable local | phenotype |
| Global pleasurable local | phenotype |
| head rush local | phenotype |
| Head rush local | phenotype |
| Hispanic | phenotype |
| Initial sensitivity | phenotype |
| initial smoking experience local | phenotype |
| Laboratory participants local | cohort |
| life-time never-smokers local | cohort |
| lung cancer | phenotype |
| major depressive disorder | phenotype |
| mania | phenotype |
| Mixed ancestry participants local | cohort |
| moderate-to-intense pleasurable rush or buzz local | phenotype |
| nausea | phenotype |
| Never-smoker local | phenotype |
| never smokers | phenotype |
| nicotine | drug |
| nicotine dependence | phenotype |
| nicotine-dependent regular smokers local | cohort |
| nicotine nasal spray | drug |
| nicotine receptor subunits local | gene |
| NIDA Genetics Consortium local | cohort |
| NRXN1 | gene |
| NRXN3 | gene |
| number of cigarettes smoked per day | phenotype |
| participants | cohort |
| pleasurable rush or buzz local | phenotype |
| Pleasurable rush or buzz local | phenotype |
| pleasurable sensations local | phenotype |
| positive early smoking experiences local | phenotype |
| present study | cohort |
| psychosis | phenotype |
| psychotropic medication | drug |
| reactivity to cigarettes during early smoking experimentation local | phenotype |
| regular nicotine-dependent smokers local | phenotype |
| regular smoking | phenotype |
| relaxation | phenotype |
| Relpair | drug |
| rs16969968 | variant |
| samples | cohort |
| sensations local | phenotype |
| smoker/never-smoker status local | phenotype |
| smoking | phenotype |
| smoking behavior | phenotype |
| Smoking Development local | phenotype |
| smoking initiation | phenotype |
| smoking persistence | phenotype |
| smoking status | phenotype |
| SNP | cohort |
| Structure | drug |
| study cohort | cohort |
| suicide | phenotype |
| tobacco use | phenotype |
| University of Michigan Nicotine Research Laboratory local | cohort |
| unpleasant sensations local | phenotype |
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